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- PDB-3q3b: 6-Amino-4-(pyrimidin-4-yl)pyridones: Novel Glycogen Synthase Kina... -

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Basic information

Entry
Database: PDB / ID: 3q3b
Title6-Amino-4-(pyrimidin-4-yl)pyridones: Novel Glycogen Synthase Kinase-3 Inhibitors
ComponentsGlycogen synthase kinase-3 beta
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of type B pancreatic cell development / negative regulation of glycogen (starch) synthase activity / negative regulation of mesenchymal stem cell differentiation / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of TORC2 signaling / negative regulation of dopaminergic neuron differentiation ...neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of type B pancreatic cell development / negative regulation of glycogen (starch) synthase activity / negative regulation of mesenchymal stem cell differentiation / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / negative regulation of TORC2 signaling / negative regulation of dopaminergic neuron differentiation / maintenance of cell polarity / positive regulation of protein localization to centrosome / positive regulation of cilium assembly / beta-catenin destruction complex / CRMPs in Sema3A signaling / heart valve development / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / tau-protein kinase / regulation of microtubule-based process / regulation of protein export from nucleus / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / Maturation of nucleoprotein / cellular response to interleukin-3 / Wnt signalosome / regulation of long-term synaptic potentiation / negative regulation of TOR signaling / negative regulation of protein localization to nucleus / Disassembly of the destruction complex and recruitment of AXIN to the membrane / AKT phosphorylates targets in the cytosol / negative regulation of calcineurin-NFAT signaling cascade / regulation of axon extension / Maturation of nucleoprotein / tau-protein kinase activity / negative regulation of epithelial to mesenchymal transition / G protein-coupled dopamine receptor signaling pathway / positive regulation of cell-matrix adhesion / regulation of axonogenesis / regulation of dendrite morphogenesis / glycogen metabolic process / ER overload response / regulation of neuron projection development / establishment of cell polarity / protein kinase A catalytic subunit binding / Constitutive Signaling by AKT1 E17K in Cancer / dynactin binding / epithelial to mesenchymal transition / Regulation of HSF1-mediated heat shock response / negative regulation of osteoblast differentiation / NF-kappaB binding / canonical Wnt signaling pathway / negative regulation of protein-containing complex assembly / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / regulation of cellular response to heat / extrinsic apoptotic signaling pathway / cellular response to retinoic acid / extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of autophagy / Transcriptional and post-translational regulation of MITF-M expression and activity / presynaptic modulation of chemical synaptic transmission / regulation of microtubule cytoskeleton organization / response to endoplasmic reticulum stress / negative regulation of cell migration / hippocampus development / positive regulation of protein export from nucleus / positive regulation of protein ubiquitination / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H2AS121 kinase activity / histone H3S57 kinase activity / excitatory postsynaptic potential / histone H3S28 kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / ribosomal protein S6 kinase activity / histone H2AT120 kinase activity / eukaryotic translation initiation factor 2alpha kinase activity / histone H2BS36 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H3S10 kinase activity / AMP-activated protein kinase activity / histone H3T11 kinase activity / histone H3T3 kinase activity / 3-phosphoinositide-dependent protein kinase activity / Ubiquitin-dependent degradation of Cyclin D / histone H3T45 kinase activity / mitochondrion organization / positive regulation of cell differentiation / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / positive regulation of protein-containing complex assembly / negative regulation of canonical Wnt signaling pathway / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2
Similarity search - Function
Glycogen synthase kinase 3, catalytic domain / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain ...Glycogen synthase kinase 3, catalytic domain / : / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-55E / Glycogen synthase kinase-3 beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsPandit, J.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2011
Title: 6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors
Authors: Coffman, K. / Brodney, M. / Cook, J. / Lanyon, L. / Pandit, J. / Sakya, S. / Schachter, J. / Tseng-Lovering, E. / Wessel, M.
History
DepositionDec 21, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 15, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jan 24, 2018Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 1.3Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Glycogen synthase kinase-3 beta
B: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)94,7204
Polymers94,1632
Non-polymers5572
Water73941
1
A: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,3602
Polymers47,0811
Non-polymers2781
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Glycogen synthase kinase-3 beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,3602
Polymers47,0811
Non-polymers2781
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)83.453, 85.647, 178.800
Angle α, β, γ (deg.)90.0, 90.0, 90.0
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Glycogen synthase kinase-3 beta / GSK-3 beta


Mass: 47081.473 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GSK3B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P49841, tau-protein kinase
#2: Chemical ChemComp-55E / 4-(4-hydroxy-3-methylphenyl)-6-phenylpyrimidin-2(5H)-one


Mass: 278.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H14N2O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 41 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.39 Å3/Da / Density % sol: 63.75 %

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.7→30 Å / Num. all: 35647 / Num. obs: 35227 / % possible obs: 99 % / Observed criterion σ(I): -3 / Redundancy: 5.2 % / Rmerge(I) obs: 0.105 / Net I/σ(I): 1.74
Reflection shellResolution: 2.7→2.8 Å / Redundancy: 5.25 % / Mean I/σ(I) obs: 2.15 / Num. unique all: 3380 / Rsym value: 0.588 / % possible all: 95.7

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Processing

Software
NameVersionClassification
CNX2000refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.7→30 Å / σ(F): 0 / Stereochemistry target values: Engh & Huber
Details: The SF file containing test flags is unfortunately lost. The only file that is available to deposit is the original reflection file (scalepack output), which does not have the FreeR flags.
RfactorNum. reflectionSelection details
Rfree0.259 1750 Random
Rwork0.228 --
all-35228 -
obs-35227 -
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--0.196 Å20 Å20 Å2
2--0.228 Å20 Å2
3----0.032 Å2
Refinement stepCycle: LAST / Resolution: 2.7→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5438 0 42 41 5521
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.011
X-RAY DIFFRACTIONc_angle_d1.578

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